Abstract
Abstract only Background: Val122Ile variant is the most common mutation causing hereditary transthyretin amyloidosis. The prevalence of Val122Ile among Hispanics/Latinos, a population with admixed genetic ancestry (African, European, Amerindian), is still unknown. Methods: We utilized genome-wide data (unweighted n=12687 adults) from the population-based HCHS/SOL to identify Val122Ile mutation. Continental proportions of African (AA), European (EA) and Amerindian (AM) ancestry were computed with an ADMIXTURE software, with thresholds set at 30%, 40%, and 50%. Complex survey analysis was employed to determine weighted frequencies of Val122Ile overall, across ancestry and across disaggregated Hispanic/Latino background groups (Cuban, Puerto Rican, Dominican, Mexican, Central American, and South American). Results: The prevalence of Val122Ile mutation in the cohort overall was 0.8%. Participants with (vs. without) Val122Ile were younger (37.3 vs. 41.6 years) and more commonly female (52.5% vs. 48.8%). Val122Ile prevalence was significantly higher among individuals with higher AA (<30% AA vs. >50% AA: 0.4% vs. 3.4%) and lower among individuals with higher EA (<30% EA vs. >50% EA: 1.7% vs. 0.8%) ( Figure 1A ). AA >50% was related with higher odds of Val122Ile mutations (OR= 7.9, 95% CI: 3.5 - 17.8) vs. AA <30%. An inverse relationship was seen with EA >50% and Val122Ile mutations (OR= 0.3, 95% CI: 0.1 - 0.6) vs. EA <30%. No statistically significant difference was found among Val122Ile by proportion of AM. Individuals with Val122Ile mutation were primarily of Dominican and Mexican descent, accounting for 33.7% and 31.7% of carriers, respectively ( Figure 1B) . Dominicans have the highest Val122Ile prevalence (2.6%) when compared to other Hispanic/Latino background groups ( Figure 1C) . Conclusion: Val122Ile mutation was mostly identified in Hispanics/Latinos at younger ages. African Ancestry is strongly correlated with Val122Ile mutations in Hispanics/Latinos with those of Dominican descent having the highest prevalence.